Portable clinical analysis system for hematocrit measurement

ABSTRACT

The present invention covers the integration and utility of accelerometer features into a clinical analysis system. For example, measurement of dynamic acceleration and orientation of a blood-testing instrument with respect to Earth&#39;s gravitational field may be used to determine reliability of a test procedure and optionally to provide corrective elements thereof.

CROSS REFERENCE TO RELATED APPLICATIONS

This application claims priority to U.S. Provisional Application No.61/738,072 filed on Dec. 17, 2012, the entirety of which is herebyincorporated by reference.

FIELD OF THE INVENTION

The invention relates to analytical testing devices. Specifically, theinvention relates to devices, systems and methods for using accelerationand orientation/inclination data in point-of-care analyte testingsystems.

BACKGROUND OF THE INVENTION

Traditionally, testing of blood or other body fluids for medicalevaluation and diagnosis was the exclusive domain of large,well-equipped central laboratories. While such laboratories offerefficient, reliable, and accurate testing of a high volume of fluidsamples, they cannot offer rapid turn-around of results to enable moreimmediate medical decision making. A medical practitioner typically mustcollect samples, transport them to a laboratory, wait for the samples tobe processed and then wait for the results to be communicated. Even inhospital settings, the handling of a sample from the patient's bedsideto the hospital laboratory produces significant delays. This problem iscompounded by the variable workload and throughput capacity of thelaboratory and the compiling and communicating of data.

The introduction of point-of-care analyte testing systems enabledpractitioners to obtain immediate test results while examining apatient, whether in the physician's office, the hospital emergency room,or at the patient's bedside. To be effective, a point-of-care analytedevice must provide error-free operation for a wide variety of tests inrelatively untrained hands. For optimum effectiveness, a real-timesystem requires minimum skill to operate, while offering maximum speedfor testing, appropriate accuracy and system reliability, as well ascost effective operation. A notable point-of-care system (The i-STAT®System, Abbott Point of Care Inc., Princeton, N.J.) is disclosed in U.S.Pat. No. 5,096,669, which comprises a disposable device, operating inconjunction with a hand-held analyzer, for performing a variety ofmeasurements on blood or other fluids.

However, unique obstacles and challenges have arisen with the advent ofpoint-of-care analyte testing systems that may impede error-freeoperation of these systems in relatively untrained hands. Specifically,in the traditional central laboratories, the analyte testing systems arelarge and placed in fixed locations within the laboratory such that theinstrumentation is rarely influenced by the effects of motion or deviceimpact. However, with point-of-care analyte testing systems, theinstrumentation is generally small and portable, e.g., a handheld mobiledevice, such that the probability of the instrumentation beinginfluenced from the effects of motion and device impacts issignificantly greater. For example, it is not uncommon for point-of-careanalyte testing systems to be dropped or jostled by relatively untrainedhands prior to or during operation. The dropping or jostling ofpoint-of-care analyte testing systems prior to or during operation mayhave disadvantageous effects on the operation of the systems.Accordingly, there exists a need in the art to improve upon the overallquality of point-of-care analyte testing systems by ameliorating theeffect of motion or device impact on the point-of-care analyte testingsystems.

SUMMARY OF THE INVENTION

In one embodiment, the present invention is directed to a portableclinical system for performing a hematocrit analysis. The systemincludes a test device comprising a hematocrit sensor and an analyzerincluding a port configured to receive the test device and a computingdevice configured to determine spatial orientation of the analyzerduring a test cycle of the test device, e.g., after the test device isinserted in the port. The computing device is further configured tocompare the determined spatial orientation to a threshold operatingspatial plane for the test device, and at least one of: (i) provide analert prompting a user to take corrective action during the test cycle,(ii) correct a result of the hematocrit analysis, and/or (iii) suppressthe result of the hematocrit analysis, when the determined spatialorientation exceeds the threshold operating spatial plane.

Additionally or alternatively, the computing device may be furtherconfigured to determine motion of the analyzer during the test cycle ofthe test device, compare the determined motion to a threshold rate ofmotion for the test device, and at least one of: (i) provide a(different) alert prompting the user to take (different) correctiveaction during the test cycle, (ii) correct the result of the hematocritanalysis, and/or (iii) suppress the result of the hematocrit analysis,when at least one of the determined spatial orientation exceeds thethreshold operating spatial plane, and/or the determined motion exceedsthe threshold rate of motion.

In addition, the computing device may be further configured to measurestatic acceleration on at least three axes of the analyzer to determinethe spatial orientation of the analyzer. In this aspect, the step ofdetermining the spatial orientation may comprises determining at leastone of roll, pitch, and/or yaw of the analyzer based on the measuredstatic acceleration on the at least three axes of the analyzer.

In addition, the analyzer preferably further comprises a processorconfigured to determine a stage of the test cycle. In this aspect, thecomputing device may be further configured to determine at least one ofthe threshold operating spatial plane based on the determined stage ofthe test cycle.

In another embodiment, a method is provided for performing a hematocritanalysis, the method comprising inserting a test device comprising ahematocrit sensor into a port of an analyzer, initiating a test cycle ofthe test device, determining spatial orientation of the analyzer duringthe test cycle of the test device, comparing the determined spatialorientation to a threshold operating spatial plane for the test device,at least one of providing an alert prompting a user to take correctiveaction during the test cycle, correcting a result of the hematocritanalysis, and/or suppressing the result of the hematocrit analysis, whenthe determined spatial orientation exceeds the threshold operatingspatial plane.

In addition, the method may further include measuring staticacceleration on at least three axes of the analyzer, and the determiningthe spatial orientation comprises determining at least one of roll,pitch, and yaw of the analyzer based on the measured static accelerationon at least three axes of the analyzer.

In addition, the method optionally includes determining a stage of thetest cycle and determining the threshold operating spatial plane basedon the determined stage of the test cycle.

In another embodiment, a method is provided for performing a hematocritanalysis, the method comprising inserting a blood sample into a testdevice comprising a conduit with a hematocrit sensor, initiating a testcycle of the test device, determining spatial orientation of the testdevice during the test cycle of the test device, comparing thedetermined spatial orientation to a threshold operating spatial planefor the test device, and at least one of providing an alert prompting auser to take corrective action during the test cycle, correcting aresult of the hematocrit analysis, and/or suppressing the result of thehematocrit analysis, when the determined spatial orientation exceeds thethreshold operating spatial plane.

In another embodiment, a system is provided for in vitro analysis, thesystem including a test device comprising at least one sensor configuredto output a signal that is partially dependent on non-homogeneity ofcells in a blood sample positioned in a region of the at least onesensor, and an analyzer comprising a port configured to receive the testdevice and a computing device configured to determine spatialorientation and motion of the analyzer during a test cycle of the testdevice. The computing device may be further configured to compare thedetermined spatial orientation to a threshold operating spatial planefor the test device, compare the determined motion to a threshold rateof motion for the test device and at least one of provide an alertprompting a user to take corrective action during the test cycle,correct a result obtained from the signal, and/or suppress the resultobtained from the signal, when at least one of the determined spatialorientation exceeds the threshold operating spatial plane, and/or thedetermined motion exceeds the threshold rate of motion.

In another embodiment, a method is provided for performing an analyticaltest. The method comprises obtaining a test device comprising at leastone sensor configured to output a signal that is partially dependent onnon-homogeneity of cells in a blood sample positioned in a region of atleast one sensor, inserting the test device in a port of an analyzer,and initiating a test cycle of the test device. The method furtherincludes determining spatial orientation and motion of the analyzerduring the test cycle of the test device and comparing the determinedspatial orientation to a threshold operating spatial plane for the testdevice. The method further includes comparing the determined motion to athreshold rate of motion for the test device, and at least one ofproviding an alert prompting a user to take corrective action during thetest cycle, correcting a result obtained from the signal, and/or thesuppressing the result obtained from the signal, when at least one ofthe determined spatial orientation exceeds the threshold operatingspatial plane, and/or the determined motion exceeds the threshold rateof motion.

In another embodiment, a portable clinical system is provided for invitro analysis. The system includes a test device comprising at leastone sensor configured to output a signal that is partially dependent onsedimentation of cells in a blood sample positioned in a region of theat least one sensor, and an analyzer comprising a port configured toreceive the test device and a computing device configured to determinespatial orientation and motion of the analyzer during a test cycle ofthe test device. The computing device may be further configured tocompare the determined spatial orientation to a threshold operatingspatial plane for the test device, compare the determined motion to athreshold rate of motion for the test device, and at least one ofproviding an alert prompting a user to take corrective action during thetest cycle, and/or correcting or suppressing a result obtained from thesignal, when at least one of the determined spatial orientation exceedsthe threshold operating spatial plane, and/or the determined motionexceeds the threshold rate of motion.

In yet another embodiment, a method is provided for performing ananalytical test. The method comprises obtaining a test device comprisingat least one sensor configured to output a signal that is partiallydependent on sedimentation of cells in a blood sample positioned in aregion of the at least one sensor, inserting the test device in a portof an analyzer, initiating a test cycle of the test device, anddetermining spatial orientation and motion of the analyzer during thetest cycle of the test device. The method further includes comparing thedetermined spatial orientation to a threshold operating spatial planefor the test device, comparing the determined motion to a threshold rateof motion for the test device, and at least one of providing an alertprompting a user to take corrective action during the test cycle, and/orcorrecting or suppressing a result obtained from the signal, when atleast one of the determined spatial orientation exceeds the thresholdoperating spatial plane, and/or the determined motion exceeds thethreshold rate of motion.

BRIEF DESCRIPTION OF THE DRAWINGS

The present invention will be better understood in view of the followingnon-limiting figures, in which:

FIG. 1A shows an exploded view of an analyzer with a cartridge insertedtherein in accordance with some aspects of the invention;

FIG. 1B shows a top view of an analyzer with a cartridge insertedtherein in accordance with some aspects of the invention;

FIG. 1C shows a bottom view of an analyzer with a cartridge insertedtherein in accordance with some aspects of the invention;

FIG. 2 shows an exploded view of a cartridge in accordance with someaspects of the invention;

FIG. 3 shows a perspective view of a analyzer in a docking station inaccordance with some aspects of the invention;

FIG. 4 is an illustrative process flow for implementing the system inaccordance with some aspects of the invention;

FIG. 5 shows roll, pitch, and yaw angles of an analyzer in accordancewith some aspects of the invention;

FIGS. 6-10 are illustrative process flows for implementing the system inaccordance with some aspects of the invention;

FIG. 11 shows vibration profiles of an analyzer in accordance with someaspects of the invention;

FIGS. 12-14 are illustrative process flows for implementing the systemin accordance with some aspects of the invention;

FIGS. 15 and 16 show acceleration profiles of an analyzer in accordancewith some aspects of the invention;

FIG. 17 shows vibration profiles of an analyzer in accordance with someaspects of the invention; and

FIG. 18 is an illustrative process flow for implementing the system inaccordance with some aspects of the invention.

DETAILED DESCRIPTION OF THE INVENTION

Introduction

The present invention relates to a handheld In-Vitro Diagnostic (IVD)instrument system including a self-contained disposable sensing deviceor cartridge and a reader or analyzer configured for use at a patientbedside. A fluid sample to be measured is drawn into a sample entryorifice or port in the cartridge and the cartridge is inserted into theanalyzer through a slotted opening or port. Measurements performed bythe analyzer are output to a display or other output device, such as aprinter or data management system via a port on the analyzer to acomputer port. Transmission can be via Wifi, Bluetooth link, infraredand the like. For example, the handheld IVD instrument system may be ofsimilar design to the systems disclosed in jointly owned U.S. Pat. No.5,096,669 and U.S. Pat. No. 7,419,821, both of which are incorporatedherein by reference in their entireties.

The analyzer is preferably designed as a mobile device such that it canbe hand carried to the location of the patient, e.g., the patient'sbedside, when a user needs to perform an analytical test, e.g., a bloodtest. As with any mobile device, occasional drops and bumps into solidsurfaces occur during handling and transport. Mechanical abuse such ascracked bezel windows, enclosures, battery doors, internal damage to theelectro-mechanical measurement module, etc., that result from devicemishandling may disadvantageously influence analytical results. Althoughforensic investigations (when analyzers are returned to the factory)reveal that mechanical abuse of analyzers is common, no precise dataexists to characterize typical operating environments of the analyzersthat may provide insight into the circumstances surrounding themechanical abuse. Accordingly, the invention, in some embodiments,provides a system for determining and recording the operatingenvironment of an analyzer.

An additional difficulty associated with performing analyte testing on ahandheld or mobile platform involves a requirement for stability or lackof motion when the analyzer is performing fluidics actuation andelectro-chemical or optical measurements. During parts of the testingcycle, precise motion actuation of the sample in the cartridge isrequired. Inertial forces due to the analyzer being moved by theoperator may create uncontrolled and disadvantageous fluid motion.However, this effect does not apply to all tests to the same extent.While some test procedures may exhibit this sensitivity, other testprocedures may be less susceptible to error resulting from inertialforces. Tests that are less susceptible to such error generally includethose that are not affected by the settling of blood cells within asample, or not affected by fluid motion or mixing. Accordingly, furtherimplementations of the invention provide a system for identifyingcircumstances during which analyte testing is subjected to inertialforces and providing counter measures to offset or eliminate the effectof the inertial forces and/or correct for the occurrence of the inertialforces.

Another difficulty that may be associated with performing analytetesting on a handheld or mobile platform involves requirements forspatial orientation of the analyzer during the measurement cycle of someanalytical tests. The spatial orientation of the analyzer can bedescribed as motion about three axes of the analyzer, defined as roll,pitch, and yaw. As cells in whole blood can at least partially sediment,e.g., on a sensor of a cartridge placed in the analyzer, and interferewith fluid flow, it may be important in some instances to properlyorient the analyzer and test cartridge with respect to Earth'sgravitational field. For example, a rate of cell sedimentation withrespect to the analyzer may be dependent on the spatial orientationand/or the motion of the reader during a test cycle. Some assays, suchas hematocrit, activated clotting time (ACT), prothrombin timeinternational normalized ratio (PT INR), and cardiac markers (e.g.,troponin I (cTnI), B-type natriuretic peptide (BNP), and creatine kinasemyocardial band (CKMB)), are more sensitive than others to this effect.

Without instrumented measurement of the dynamic acceleration and theorientation of the analyzer, the operator may be relied upon to ensurethat the analyzer is stable and properly positioned on a horizontalsurface for substantially the entire duration of the measurement cycle.The time period required for completing analytical tests may range, forexample, from approximately 2 to 20 minutes. In a busy hospitalenvironment, it may be desirable to free up the healthcare staff fromattending to the analyzer while the test is running and allow the staffto receive feedback if the analyzer is either unstable, improperlypositioned, or has been moved during the test cycle. Accordingly,further implementations of the invention provide a system foridentifying circumstances during which the analyte testing is subjectedto inertial forces and providing notification of the detection of theinertial forces, counter measurements to offset or eliminate the effectof the inertial forces, and/or correct for the occurrence of theinertial forces. More specifically, one embodiment of the presentinvention uses inertial data collected by on-board accelerometers todetect, and react to, disadvantageous motion of the analyzer duringcritical measurement cycle phases; provide positioning information tothe user with respect to Earth's gravity; and provide otherfunctionalities made possible by the knowledge of inertial information.

IVD Instrument System

As will be appreciated by one skilled in the art, aspects of the presentinvention may be embodied as a system, method or computer programproduct. Accordingly, aspects of the present invention may take the formof an entirely hardware embodiment, an entirely software embodiment(including firmware, resident software, micro-code, etc.) or anembodiment combining software and hardware aspects that may allgenerally be referred to herein as a “circuit,” “module” or “system.”Furthermore, aspects of the present invention may take the form of acomputer program product embodied in one or more non-transitory computerreadable storage medium(s) having computer readable program codeembodied thereon.

FIGS. 1A-1C depict an analyzer 10 with a base 11 and a cartridge 12(e.g., a test device) inserted within a universal port 13 of theanalyzer 10, e.g., an i-STATT™ handheld analyzer with an i-STATT™cartridge inserted therein, as described in jointly owned U.S. Pat. No.5,096,669 and U.S. Pat. No. 7,419,821. The cartridge 12 includes asample entry port 45 that is substantially aligned to a plane parallelto a horizontal plane of the base 11. The analyzer 10 includes a display14, a battery pack 15, and a reader 16, e.g., a 2D barcode scanner. Theanalyzer 10 further includes a computing device 17 that interfaces withvarious cartridges 12 via the port 13.

The computing device 17 can be resident on a network infrastructure,e.g., a hospital intranet. The computing device 17 also preferablyincludes a processor, memory, an I/O interface, and a bus. The busprovides a communications link between each of the components in thecomputing device 17. The memory can include local memory employed duringactual execution of program code, bulk storage, and cache memories thatprovide temporary storage of at least some program code in order toreduce the number of times code must be retrieved from bulk storageduring execution. In addition, the computing device 17 preferablyincludes random access memory (RAM), a read-only memory (ROM), and anoperating system (O/S).

In general, the processor is configured to execute computer programcode, which can be stored in the memory. While executing the computerprogram code, the processor can read and/or write data to/from memory.The program code executes the processes of the invention. For example,in accordance with some aspects of the invention, the program codecontrols a measurement module 20 and one or more accelerometers 25,which perform the processes described herein. In additional oralternative embodiments, the program code may also be configured tocontrol one or more on-board sensors additional to that of theaccelerometers 25, e.g., a temperature sensor, an ambient light sensor,a barometric pressure sensor, an imaging camera, etc, which may be usedfor various functions of the analyzer 10. The measurement module 20 canbe implemented as one or more program code in the program control storedin the memory as separate or combined modules. Additionally, themeasurement module 20 may be implemented as separate dedicatedprocessors, a single processor, or several processors to provide thefunction of the module.

The measurement module 20 is configured to interact with the cartridge12 in multiple ways. For example, the measurement module 20 maydetermine the type of cartridge 12 inserted into the analyzer 10 usingfor example the imaging camera to capture data from a bar codepositioned on the cartridge, secure the cartridge 12 mechanically,establish electrical connections with sensors in the cartridge 12,regulate the temperature of the cartridge 12 during a test cycle usingfor example the temperature sensor, actuate calibration and samplefluids according to pre-established cycles, and optionally acquireimages using for example the imaging camera of areas located on thecartridge 12, e.g., the underside of the cartridge.

To this extent, the functionality provided by the computing device 17 ofthe analyzer 10 can be implemented by a computing article of manufacturethat includes any combination of general and/or specific purposehardware and/or computer program code. In each embodiment, the programcode and hardware can be created using standard programming andengineering techniques, respectively.

The accelerometer 25 is mounted on an electronic board 30 within theanalyzer 10. The measurement module 20 and the electronic board 30 areboth secured in the analyzer 10 with fasteners and aligned withreference surfaces. The measurement module 20 is configured to preciselyand securely position the cartridge 12 in place when the cartridge 12 isinterfaced with measurement module 20 through the port 13. Therefore, inaccordance with some aspects of the invention the computing device isconfigured to determine the orientation and acceleration of the analyzerby itself or both the analyzer 10 and the cartridge 12 (when insertedinto the measurement module 20) by means of the accelerometer 25.

The one or more accelerometers 25 are electromechanical devices thatmeasure acceleration. Acceleration is the rate at which the velocity ofa body changes over time. Proper acceleration is the physicalacceleration experienced by an object. Accelerometers are devices thatmeasure proper acceleration. Therefore, the acceleration measured by anaccelerometer is not necessarily the rate of change of velocity. Forexample, an accelerometer at rest on the surface of the earth willmeasure an acceleration of g=9.81 m/s². Accelerometers in free fall willmeasure zero acceleration. The term “acceleration” as used hereinindicates “proper acceleration” or acceleration measured by theaccelerometer.

Acceleration forces may be static, like the constant force of gravitypulling objects towards the Earth's surface, or they may be dynamic,e.g., caused by moving or vibrating the accelerometer. By measuring theamount of static acceleration due to gravity, it is possible todetermine the angle the device is tilted at with respect to Earth'sgravitational field. By sensing the amount of dynamic acceleration, itis possible to analyze the direction or manner in which the device ismoving. The operating principle of the accelerometer can be described asa simple mass supported on a damped spring. The mass is displaced whenthe accelerometer experiences acceleration. Measurement of thedisplacement of the mass is used to derive the acceleration.Piezoelectric, piezoresistive, and capacitive components are used incommercially available accelerometers to convert displacement into anelectrical signal. Other forms of accelerometers may also be used.

Several accelerometers, e.g., ADXL345 (Analog Devices, Inc.), MMA7260Q(Freescale Semiconductor, Inc.), and H48C (Hitachi) are commerciallyavailable and may be implemented in the present invention. For example,the ADXL345 includes a small, thin, ultra-low power, 3-axisaccelerometer with high resolution (13-bit) measurement at up to ±16 g.The ADXL345 may be well suited for mobile device applications. TheADXL345 measures the static acceleration of gravity in tilt-sensingapplications, as well as dynamic acceleration resulting from motion orshock. The ADXL345's high resolution (3.9 mg/LSB) enables measurement ofinclination changes less than 1.0°. Threshold values can be assigned forboth dynamic acceleration and angle deviation from rest position.However, it should be understood that the present invention is notlimited to these exemplary accelerometers.

FIG. 2 shows an exploded view of cartridge 12 as described in jointlyowned U.S. Patent Application Publication No. 2011/0150705 and U.S.patent application Ser. No. 13/530,501. The cartridge 12 comprises asample entry port 45, at least one sensor 50 (e.g., an electrochemicalsensor, an immunosensor, a hematocrit sensor, a conductivity sensor,etc.), and a pouch 55 containing a fluid, e.g., asensor-standardization, calibration fluid, and/or wash fluid. The atleast one sensor 50 is substantially aligned to a plane parallel to ahorizontal plane of the base of the analyzer. A recessed region 60 ofthe cartridge 12 preferably includes a spike 63 configured to rupturethe pouch 55, upon application of a force upon the pouch 55, forexample, by the analyzer 10 (shown in FIG. 1). Once the pouch 55 isruptured, the system is configured to deliver the fluid contents fromthe pouch 55 into a conduit 65. Movement of the fluid into and throughthe conduit 65 and to a sensor region 70 (e.g., a conduit comprising theat least one sensor 50 and a sensing reagent for the sensor) may beeffected by a pump, e.g., a pneumatic pump connected to the conduit 65.Preferably, the pneumatic pump comprises a displaceable membrane 75. Inthe embodiment shown in FIG. 2, the cartridge 12 or test device isconfigured to pump fluid via the displaceable membrane 75 from theruptured pouch 55 and the sample entry port 45 through the conduit 65and over the sensor region 70. The at least one sensor 50 generateselectric signals based on a concentration of specific chemical speciesin the sample, e.g., performs an immunoassay on a blood sample from apatient.

The analytes/properties to which the at least one sensor respondsgenerally may be selected from among hematocrit, troponin, CKMB, BNP,beta human chorionic gonadotropin (bHCG), carbon dioxide partialpressure (pCO₂), partial pressure oxygen (pO₂), pH, PT, ACT, activatedpartial thromboplastin time (APTT), sodium, potassium, chloride,calcium, urea, glucose, creatinine, lactate, oxygen, and carbon dioxide,thyroid stimulating hormone, parathyroid hormone, D-dimer, prostatespecific antibody and the like, and combinations thereof. Preferably,the analyte is tested in a liquid sample that is whole blood, howeverother samples can be used including blood, serum, plasma, urine,cerebrospinal fluid, saliva and amended forms thereof. Amendments caninclude diluents and reagents such as anticoagulants and the like.

FIGS. 4, 6-10, 12-14, and 18 show exemplary flowcharts for performingthe process steps of the present invention. The steps of FIGS. 4, 6-10,12-14, and 18 may be implemented using the computing device describedabove with respect to FIGS. 1A-1C. Specifically, the flowcharts in FIGS.4, 6-10, 12-14, and 18 illustrate the architecture, functionality, andoperation of possible implementations of the systems, methods andcomputer program products according to several embodiments of thepresent invention. In this regard, each block in the flowcharts mayrepresent a module, segment, or portion of code, which comprises one ormore executable instructions for implementing the specified logicalfunction(s). It should also be noted that, in some alternativeimplementations, the functions noted in the blocks may occur out of theorder noted in the figure. For example, two blocks shown in successionmay, in fact, be executed substantially concurrently, or the blocks maysometimes be executed in the reverse order, depending upon thefunctionality involved. It will also be noted that each block of theflowchart illustrations, and combinations of blocks in the flowchartillustrations, can be implemented by special purpose hardware-basedsystems that perform the specified functions or acts, or combinations ofspecial purpose hardware and computer instructions.

Detection of Improper Orientation During Testing

In one embodiment of the present invention, the computing device isconfigured to measure static acceleration using the accelerometer andformulate a determination on whether one or more actions should betriggered based on the measured static acceleration. As discussed above,in some embodiments, the accelerometer is configured to measureinclination changes (e.g., inclination changes of less than about 1.0°)of the analyzer by itself or of both the analyzer and the cartridgeduring a test cycle after the cartridge has been inserted into themeasurement module. Since some assays are sensitive to inclinationchanges (e.g., hematocrit, ACT, PT INR, and cardiac markers such ascTnI, BNP, and CKMB), it is important to keep the analyzer properlypositioned on a flat horizontal surface for substantially the entireduration of a test cycle for these analytes.

For example, when not in use, analyzer 10 may be docked in adownloader/recharge station (base station) 85, as shown in FIG. 3. Thebase station 85 may be configurable as a bench top (horizontal) orwall-mount (vertical) unit. In the wall-mount configuration, theanalyzer is positioned vertically and therefore should not be used fortesting unless the orientation of the reader is modified such that thecartridge is substantially horizontal while the reader is in thevertical position. The accelerometer can detect the angle of theanalyzer and send the angle measurement information to the computingdevice. By comparing the angle of the analyzer to at least onepredetermined threshold (e.g., a first threshold related to the benchtop (horizontal) configuration of the docked analyzer 10 and/or a secondthreshold related to the wall-mount (vertical) configuration of thedocked analyzer), the computing device can trigger one or more actions,e.g., authorize or disable testing and/or display a warning message tothe operator. Accordingly, some aspects of the invention provide systemsand processes for monitoring inclination changes of the analyzer duringoperation to ensure that the analyzer remains in a substantiallyhorizontal position.

As shown in FIG. 4, a process 100 is provided for monitoring inclinationchanges of the analyzer during operation, and triggering one or moreactions (e.g., counter measures) if the inclination changes exceed oneor more predetermined thresholds. At step 105, a determination is madeas to whether the analyzer has been requested to start a test cycle foran analytical test. For example, the computing device using themeasurement module is configured to make a determination as to whetheran operator has inserted a cartridge into the port of the analyzer, andwhether the analyzer has been prompted, e.g., via the I/O interface, toperform an analytical test using the cartridge. At step 110,acceleration data is collected during the test cycle. For example, theaccelerometer may be configured to generate static acceleration dataalong up to three axes (x, y, z).

At step 115, the acceleration data is used to determine the spatialorientation of the analyzer and the cartridge during the test cycle. Forexample, the computing device and/or the accelerometer may be configuredto use the acceleration data along one or more of the three axes tocalculate corresponding angular measurements for the one or more axes ofthe analyzer such that the spatial orientation of the analyzer may bedetermined with respect to roll, pitch, and yaw of the analyzer, asshown in FIG. 5.

As further shown in FIG. 4, at step 120, the determined spatialorientation of the analyzer is compared to a threshold operating spatialplane, e.g., ±20° of a horizontal plane of the base of the analyzer,more preferably ±15° of a horizontal plane, even more preferably ±10° ofa horizontal plane. For example, the computing device may be configuredto compare the spatial orientation of the analyzer to one or morepredetermined threshold values stored in the memory (e.g., the valuesmay be stored in a table or database). The predetermined thresholdvalues may be independent of or dependent on the type of cartridgeinserted into the analyzer. In additional embodiments of the presentinvention, the computing device may be configured to compare: (i) theroll of the analyzer to a predetermined threshold roll; (ii) the pitchof the analyzer to a predetermined threshold pitch; and (iii) the yaw ofthe analyzer to a predetermined threshold yaw, or, alternatively, acomposite threshold of two or three values.

At step 125, if the spatial orientation of the analyzer exceeds thethreshold operating spatial plane, one or more actions may be triggered.Specifically, if the computing device determines that the spatialorientation of the analyzer exceeds the threshold operating spatialplan, then the computing device may prompt the operator to takecorrective action. For example, the computing device may send anotification alert to the display of the analyzer that instructs and/orillustrates corrective action including required movement of theanalyzer with regard to the threshold operating spatial plane in orderto prompt the operator into correcting the spatial orientation of theanalyzer back within the threshold operating spatial plane during thetest cycle.

Additionally or alternatively, the computing device may be configured tosuppress a result of the analytical test if the computing devicedetermines that the spatial orientation of the analyzer exceeds thethreshold operating spatial plan. For example, the computing device maybe configured to determine that the spatial orientation of the analyzerexceeded the threshold operating spatial plan for a predetermined amountof time and/or by a predetermined margin, and thus the integrity of theanalytical test is compromised beyond correction and the test resultshould be suppressed. Furthermore, the computing device may also beconfigured to log the event of the calculated angular measurementsexceeding the threshold values in a history log available for futureuse; interrupt or modify the test cycle in progress; lock the analyzerfrom completing or performing the analytical test, and/or correct thetest result as discussed in further detail herein.

In the additional embodiments of the present invention, if the computingdevice determines that the determined roll of the analyzer exceeds thethreshold roll, the determined pitch of the analyzer exceeds thethreshold pitch, and/or the determined yaw of the analyzer exceeds thethreshold yaw or composite threshold, then the computing device maytrigger one or more actions, e.g., providing the alert prompting theuser to take the corrective action during the test cycle, and/orsuppressing the result of the analytical test.

At step 130, if the spatial orientation of the analyzer does not exceedthe threshold operating spatial plane, the process continues monitoringstarting at step 110 for the duration of the test cycle.

As with the previous embodiments described herein, one or more steps inthe process described in connection with FIG. 4 may occur simultaneouslyor substantially simultaneously with other process steps and/or theorder of the steps may be modified.

Detection of Improper Motion During Testing

In another embodiment, the invention pertains to a method andcorresponding computing system and device configured to measure dynamicacceleration using the accelerometer and formulate a determination onwhether one or more actions should be triggered based on the measureddynamic acceleration. In this aspect, the accelerometer is configured tomeasure the dynamic acceleration of the analyzer by itself or of boththe analyzer and the cartridge, i.e., after the cartridge is insertedinto the measurement module. Since some assays are sensitive to dynamicacceleration (e.g., immunometric testing), it is important to minimizethe effects of motion for substantially the entire duration of a testcycle for these types of assays. Accordingly, in some aspects, theinvention provides systems and processes for monitoring the motion ofthe analyzer during operation to ensure that the analyzer remainssubstantially motionless.

As shown in FIG. 6, a process 200 is provided for monitoring the motionof the analyzer during operation and executing counter measures (triggerone or more actions) if the motion exceeds one or more predeterminedthresholds. At step 205, a determination is made as to whether theanalyzer has been requested to start a test cycle for an analyticaltest. For example, the computing device using the measurement module maybe configured to make a determination as to whether an operator hasinserted a cartridge into the port of the analyzer, and whether theanalyzer has been prompted, e.g., via the I/O interface, to perform ananalytical test using the cartridge. At step 210, acceleration data iscollected during the test cycle. For example, the accelerometer may beconfigured to generate dynamic acceleration data.

At step 215, the acceleration data is used to determine whether there isany movement of the analyzer and/or the cartridge during the test cycle.For example, the computing device and/or the accelerometer may beconfigured to determine whether inertial forces are being applied to theanalyzer through dynamic acceleration in one or more directions.Furthermore, the computing device and/or the accelerometer may beconfigured to calculate a rate of motion for the analyzer based on theacceleration data.

At step 220, the determined motion and/or rate of motion of the analyzeris compared to a predetermined threshold, e.g., a threshold rate ofmotion of about 50 meters/second², for the analyzer. For example, thecomputing device may be configured to compare the motion and/or rate ofmotion of the analyzer to one or more predetermined threshold valuesstored in the memory, e.g., the one or more predetermined thresholds maybe stored in a table or database. The predetermined threshold value maybe independent of or dependent on the type of cartridge inserted intothe analyzer.

At step 225, if the motion and/or rate of motion of the analyzer exceedsthe threshold rate of motion, one or more actions may be triggered.Specifically, if the computing device determines that the motion and/orrate of motion of the analyzer exceeds the threshold rate of motion,then the computing device may prompt the operator to take correctiveaction. For example, the computing device may send a notification alertto the display of the analyzer that instructs and/or illustratescorrective action including the cessation or deceleration of movement ofthe analyzer with regard to the threshold rate of motion in order toprompt the operator into correcting the motion of the analyzer below thethreshold rate of motion.

Additionally or alternatively, the computing device may be configured tosuppress a result of the analytical test if the computing devicedetermines that the motion and/or rate of motion of the analyzer exceedsthe threshold rate of motion. For example, the computing device may beconfigured to determine whether the motion and/or rate of motion of theanalyzer exceeds the threshold rate of motion for a predetermined amountof time and/or by a predetermined margin, and thus whether the integrityof the analytical test has been compromised beyond correction, andwhether the test result should be suppressed. Furthermore, the computingdevice may also be configured to log the event of the motion and/or rateof motion exceeding the threshold value in a history log available forfuture use; interrupt or modify the test cycle in progress; and/orcorrect the test result as discussed in further detail herein.

At step 230, if the motion and/or rate of motion of the analyzer doesnot exceed the threshold rate of motion, the process continuesmonitoring starting at step 210 for the duration of the test cycle.

As should be understood by one of skill, the processes 100 and 200 maybe performed separate of one another or as a single process. Theprocesses 100 and 200 may be performed sequentially or simultaneously.Further, the processes 100 and 200 may be performed independent of ordependent on the type of cartridge inserted into the analyzer. Forexample, in the instance that an immunometric cartridge is detectedinserted within the port of the analyzer, the process 200 may be theonly process executed, whereas in the instance that a hematocritcartridge is detected inserted within the port of the analyzer, theprocess 100 may be the only process executed. Advantageously, this maysave on computations by the processor and preserve battery life of theanalyzer.

Detection of Improper Spatial Orientation and/or Motion During SpecificStages of the Test Cycle

In another embodiment, the processes of the invention and relatedsystems may further include a step of formulating determinations basedon a stage of the test cycle. For example, during a test cycle, atypical cartridge may be performing a number of actions or steps toultimately sense a target analyte within a sample. These steps mayinclude among others (i) actuation steps in which fluid is being movedfrom one location of the cartridge to another; (ii) incubation steps inwhich reactions are being promoted to proceed; (iii) mixing steps inwhich different fluids and reagents are being combined; (iv) washingsteps in which fluids are being rinsed from a particular location, e.g.,the sensor region; and (v) detection steps in which analytes and/orsignals are being read or detected. The threshold values used todetermine whether one or more actions should be triggered may be stagespecific and/or the triggered one or more actions may be stage specific.Accordingly, in some aspects, the invention relates to systems andprocesses for monitoring the spatial orientation and/or motion of theanalyzer during one or more stages, optionally each stage, of the testcycle, and formulating determinations based on the stage of the testcycle in which one or more events occur.

As shown in FIG. 7, the process 300 may start at step 305 where adetermination is made as to whether the analyzer has been requested tostart a test cycle for an analytical test, as described with respect toFIGS. 4 and 6. At step 310, acceleration data is collected during thetest cycle. For example, the accelerometer may be configured to collectstatic and/or dynamic acceleration data. In additional embodiments ofthe present invention, the computing device and/or the accelerometer maybe configured to determine the roll, pitch, and/or yaw of the analyzer,as discussed above with respect to FIG. 4.

At step 315, the acceleration data is used to determine the spatialorientation of the analyzer and/or whether there is any movement of theanalyzer during the test cycle. At step 320, a stage of the test cycleis determined. For example, the computing device may be configured todetermine at what stage of the test cycle (e.g., actuation stage,incubation stage, mixing stage, wash stage, or detection stage) theanalyzer and cartridge are currently functioning. At step 325, athreshold operating spatial plane and/or threshold rate of motion aredetermined based on the determined stage of the test cycle. For example,the computing device may be configured to access a table or database andselect the threshold operating spatial plane and/or the threshold rateof motion based on the determined stage of the test cycle. In additionalembodiments of the present invention, the computing device may beconfigured to determine a predetermined threshold roll, a predeterminedthreshold pitch, and/or a predetermined threshold yaw based on thedetermined stage of the test cycle.

At step 330, the determined spatial orientation and/or motion and/orrate of motion of the analyzer is compared to the determinedthreshold(s) selected based on the current stage of the test cycle. Inadditional embodiments of the present invention, the computing devicemay be configured to compare the roll of the analyzer to thepredetermined threshold roll, the pitch of the analyzer to thepredetermined threshold pitch, and/or the yaw of the analyzer to thepredetermined threshold yaw or composite threshold, based on thedetermined stage of the test cycle.

At step 335, if the spatial orientation and/or motion and/or rate ofmotion of the analyzer exceeds at least one of the determinedthreshold(s), one or more actions may be triggered. Specifically, if thecomputing device determines that the spatial orientation and/or motionand/or rate of motion of the analyzer exceeds at least one of thedetermined threshold(s), then the computing device may send anotification to the operator and/or prompt the operator to takecorrective action. Furthermore, the computing device may also beconfigured to log the event in a history log available for future use;interrupt or modify the test cycle in progress; and/or correct the testresult as discussed in further detail herein.

At step 340, if the spatial orientation and/or motion and/or rate ofmotion of the analyzer does not exceed determined threshold(s), theprocess continues monitoring starting at step 310 for the duration ofthe test cycle.

As with the previous embodiments described herein, one or more steps inthe process described in connection with FIG. 7 may occur simultaneouslyor substantially simultaneously with other process steps and/or theorder of the steps may be modified. For example, the step of determiningthe stage of the test cycle may occur before, concurrently with, orafter the step of determining spatial orientation and/or motion of theanalyzer.

Detection of Improper Spatial Orientation and/or Motion forSelf-Correction

In another embodiment of the present invention, the processes describedherein may further include correcting a signal from at least one sensorbased on whether an improper spatial orientation and/or motion of theanalyzer has been detected and optionally on the relative degree of theimproper spatial orientation and/or motion of the analyzer. For example,the processes may include determining a correction factor associatedwith the spatial orientation and/or motion of the analyzer, e.g., from alook up table, correction algorithm, or the like, and applying thecorrection factor to a signal generated by the sensor to produce acorrected signal.

In alternative embodiments, the processes described herein may alsoinclude correcting or modifying at least one process of the test cycle,e.g., modifying a timing of the test cycle, based on whether improperspatial orientation and/or motion of the analyzer has been detected. Forexample, the process may include a step of determining improper spatialorientation and/or motion of the analyzer, and modifying an incubationstage of the test cycle such that a test analyte and a signal antibodyare in contact with one another for a longer (or shorter) period oftime. Accordingly, in some aspects, the invention relates to systems andprocesses for monitoring the spatial orientation and/or motion of theanalyzer during the test cycle, and self-correcting an analyte signal orat least one process step of the test cycle, e.g., incubation period, ifthe spatial orientation and/or motion of the analyzer exceedspredetermined thresholds.

As shown in FIG. 8, the process 400 may start at step 405 where adetermination is made as to whether the analyzer has been requested tostart a test cycle for an analytical test, as described with respect toFIGS. 4 and 6. At step 410, acceleration data is collected during thetest cycle. For example, the accelerometer may be configured to collectstatic and/or dynamic acceleration data. In additional embodiments ofthe present invention, the computing device and/or the accelerometer maybe configured to determine the roll, pitch, and/or yaw of the analyzer,as discussed above with respect to FIG. 4.

At step 415, the acceleration data is used to determine the spatialorientation of the analyzer and/or whether there is any movement of theanalyzer during the test cycle. At step 420, the determined spatialorientation and/or motion and/or rate of motion of the analyzer iscompared to predetermined threshold(s). In the additional embodiments ofthe present invention, the computing device may be configured to comparethe roll of the analyzer to a predetermined threshold roll, the pitch ofthe analyzer to a predetermined threshold pitch, and/or the yaw of theanalyzer to a predetermined threshold yaw, or alternatively a compositethreshold.

At step 425, if the spatial orientation and/or motion and/or rate ofmotion of the analyzer exceed the determined threshold(s), one or moreactions may be triggered. Specifically, if the computing devicedetermines that the spatial orientation and/or motion and/or rate ofmotion of the analyzer exceeds at least one of the determinedthreshold(s), then the computing device may at step 430 determine acorrection factor associated with the spatial orientation and/or motionof the analyzer, e.g., from a look up table, correction algorithm, orthe like, and, at step 435, apply the correction factor to a signalgenerated by the sensor to produce a corrected signal. The correctionfactor may include a blood non-homogeneity correction factor, a bloodcell sedimentation correction factor, and/or a blood motion factor. Ablood non-homogeneity factor may be determined experimentally by runninga set of test devices at different pitch orientations, e.g. zerodegrees, five degrees, ten degrees . . . ninety degrees (or some subsetthereof), and recording the response of a given sensor, e.g., hematocit.This may be repeated for yaw and roll and also for a range of analyteconcentrations, e.g., hematocrit concentrations, zero, 20%, 40% and 60%.In this way a family of curves relating “true analyte” at zero degreesversus “measured analyte” is obtained as a function of orientation. Byembedding an algorithm derived from these data into the instrument, theinstrument can then determine the correction factor to apply for anygiven measured orientation. Where the non-homogeneity relates to redblood cells, the correction factor addresses sedimentation. With respectto a blood motion factor, this is determined experimentally by running aset of test devices while applying different motions to the instrument(using robotics programmed to repeat a controlled motion) and recordingthe response of a given sensor, e.g. troponin. This is repeated over arange of analyte concentrations, and again a family of curves relating“true analyte” (zero motion) versus “measured analyte” is obtained as afunction of various motions. By embedding an algorithm derived fromthese data into the instrument, the instrument can then determine amotion and find the nearest embedded model analog to that motion. Alook-up table is then used to find a correction factor to apply for anygiven recorded motion.

In alternative embodiments, steps 430 and 435 may include correctingand/or modifying at least one process step of the test cycle. Forexample, the computing device may be configured to modify the timing ofthe test cycle upon the determination that the spatial orientationand/or motion and/or rate of motion of the analyzer exceeds at least oneof the determined threshold(s).

At step 440, if the spatial orientation and/or motion and/or rate ofmotion of the analyzer do not exceed at least one of the predeterminedthreshold(s), the process continues monitoring starting at step 410 forthe duration of the test cycle.

As with the previous embodiments described herein, one or more steps inthe process described in connection with FIG. 8 may occur simultaneouslyor substantially simultaneously with other process steps and/or theorder of the steps may be modified.

Operation and Verification of the Analyzer

As discussed in detail herein, acceleration data collected by theaccelerometer can be used to determine the spatial orientation andmotion of the analyzer during a testing cycle that can potentiallycompromise the integrity of an analytical test being performed by theanalyzer. Some embodiments of the invention, however, are not limited tocollecting acceleration data only during a testing cycle. For example,acceleration data may be collected by the accelerometer intermittentlyor continuously throughout the day, and optionally including during thetesting cycle operation.

The detected spatial orientation and mechanical shock or vibrationoutside of the testing cycle operation may be used to determine anoperational state of the analyzer, e.g., whether the analyzer is in useor in a state of rest, character recognized input for the analyzer, anoperational status of the analyzer, e.g., whether the analyzer isperforming a function properly, and/or the analyzer is damaged.Specifically, the computing device may be configured to analyze theacceleration data generated by the accelerometer and compare theacceleration data levels with predetermined thresholds stored in thememory. A fall onto a hard surface, for example, can be detected byidentifying free fall followed by very high deceleration generated bythe impact. For example, the ADXL345 accelerometer features a built-infree fall detection. The computing device can monitor the sequence ofevents (e.g., a free fall followed by a high rate of deceleration) andtrigger one or more actions. These actions may include; (i) logging theevent in a history log available for future use (e.g., during repair ofmalfunctioning analyzers); (ii) displaying a warning or serviceindicator message for the operator; (iii) locking the analyzer untilQuality Control is completed successfully (per procedures at usersites); (iv) performing internal diagnostics; (v) communicating,optionally via internet, the status of the analyzer to a central commandservice portal with the ability to place an automated request for areplacement unit if fault is detected, and/or; (vi) interrupting ormodifying the test cycle in progress. Other similar functions will beapparent to those skilled in the art of point of care blood testing. Forexample, during product shipment, if the battery is connected to theanalyzer, a log of shocks and vibration due to transportation can begenerated. Upon delivery of the analyzer, the data corresponding to theshipping period can be examined to determine if shipping damage hasoccurred.

Power Management

In one embodiment, the analyzer may be a battery-powered handheld devicefor use in point-of-care analyte testing. The analyzer should be readyfor use quickly and reliably. Therefore, power management of theanalyzer is an important consideration to achieve maximum uptime andreliability. In particular, the analyzer can be placed in various statesthat achieve different levels of power savings, e.g., standby, sleep,and power off, based on the acceleration data received from theaccelerometer.

Furthermore, depending on the power saving mode, wake-up times may bedifferent. Unless the analyzer is always ON, the operator has to waitfor the duration of the wake up to start testing operations. Therefore,the acceleration data can also be used to reduce the wait time.Accordingly, some aspects of the present invention provide a system andprocess for determining when to place the analyzer in different levelsof power saving and when to wake up the analyzer for anticipatedoperation.

As shown in FIG. 9, the process 500 may start at step 505 whereacceleration data is collected. For example, the accelerometer may beconfigured to collect static and/or dynamic acceleration dataintermittently or continuously throughout the day. At step 510, theacceleration data is used to determine the spatial orientation of theanalyzer and/or whether there is any movement of the analyzer. At step515, the determined spatial orientation and/or motion and/or rate ofmotion of the analyzer is compared to predetermined threshold(s). Forexample, the spatial orientation and/or motion and/or rate of motion ofthe analyzer are compared to predetermined threshold(s) stored in thememory to determine whether the analyzer is in motion or not.

At step 520, if the spatial orientation and/or motion and/or rate ofmotion of the analyzer exceed at least one of the determinedthreshold(s), one or more actions (e.g., a first action or first set ofactions) may be triggered. For example, if the computing devicedetermines that the spatial orientation and/or motion and/or rate ofmotion of the analyzer exceed at least one of the determinedthreshold(s), then the computing device may determine that the analyzeris being moved and/or transported and initiate a power ON cycleconcurrently or soon thereafter (e.g., once the analyzer is picked up bythe operator) such that the analyzer is available for a subsequentanticipated operation.

At step 525, if the spatial orientation and/or motion and/or rate ofmotion of the analyzer do not exceed at least one of the determinedthreshold(s), one or more actions (e.g., a second action or second setof actions) may be triggered. For example, if the spatial orientationand/or motion and/or rate of motion of the analyzer do not exceed atleast one of the predetermined threshold(s), then the computing devicemay determine that the analyzer has been left unattended in a restingposition for a preset (or configurable) period of time and initiate apre-set power saving mode(s) dependent on or independent of the periodof time the analyzer has been left in the undisturbed position.

Detection of Proper Insertion of Cartridge

In one embodiment, the analyzer comprises electromechanical features fordocking and locking a cartridge within the port, as discussed above withrespect to FIGS. 1A-1C. Specifically, a cartridge latch within theanalyzer may engage a feature located at a bottom of the cartridge and aspring action pushes the cartridge all the way into the port whencartridge is inserted into the port of the measurement module.Advantageously, these electromechanical features have several benefitsincluding ensuring that the cartridge is engaged in the proper position,preventing the cartridge from moving during the test cycle, andproviding tactile feedback to the operator indicating that the cartridgeis properly inserted within the analyzer.

Furthermore, the measurement module may also be equipped with anelectromechanical contact switch triggered by the cartridge when thecartridge is inserted in the correct position in the port. The computingdevice monitors the switch status and initiates the cartridge test cyclewhen the switch is activated. Similarly, the computing device may beconfigured to detect removal of the cartridge. However, theelectromechanical features described above may require additional parts(e.g., follower arm, electromechanical switch, cables, and connectors)and additional features on the measurement module mechanical housing toguide the follower arm and position the switch. These parts and featuresmay be potentially eliminated by using acceleration data.

For example, engagement of a cartridge latch when the cartridge is fullyinserted in the analyzer creates a signature vibration profile that canbe detected by the accelerometer(s). The computing device may beconfigured to compare the vibration profile for an inserted cartridge toa pre-established vibration profile stored in the memory to determinewhether proper or full engagement of the cartridge has occurred.Accordingly, aspects of the present invention provide a system andprocesses for determining whether the cartridge is inserted properlyinto the analyzer using vibration profiles.

As shown in FIG. 10, the process 600 may start at step 605 whereacceleration data is collected. For example, the accelerometer may beconfigured to collect static and/or dynamic acceleration dataintermittently or continuously throughout the day. At step 610, theinsertion of a cartridge into the port is detected. For example, anoperator may engage a cartridge within the port of the measurementmodule such that an analytical test can be performed on a sample withinthe cartridge. The computing device may be configured to detect theinsertion, e.g., sensing the engagement of the cartridge latch. At step615, the acceleration data is used to create an acceleration profile forthe insertion of the cartridge. For example, the computing device may beconfigured to use the acceleration data collected during the insertionof cartridge, which comprises vibrations characteristic of theelectromechanical interaction between the cartridge and the analyzerduring the insertion, to create a current vibration profile 650 (see,e.g., FIG. 11) for the insertion of the cartridge.

At step 620, the current vibration profile 650 for the insertion of thecartridge may be compared to a pre-established vibration profile 655(e.g., a vibration profile pre-recorded for a proper insertion of acartridge with the same analyzer). For example, as shown in FIG. 11, thecomputing device may be configured to compare the current vibrationprofile 650 to the pre-established vibration profile 655 and a band ofexpected variation 660 (e.g., a predetermined range of acceptablevariation) stored in the memory to determine whether the cartridge isinserted properly or fully into the analyzer.

Optionally at step 625, an internal barcode reader (e.g., the imagingcamera as discussed with respect to FIGS. 1A-1C) located in themeasurement module of the analyzer can image the cartridge to confirmthat the cartridge is correctly positioned in the port (see, e.g., U.S.Provisional Patent Application No. 61/579,816, which is incorporatedherein by reference in its entirety). The image acquired by the barcodereader can be compared by the computing device with a reference image.Registration of the acquired image with the reference image previouslystored in memory allows confirming that test cartridges are in theproper position. Optionally, features (e.g., 1-D or 2-D barcode,geometric feature, etc.) dedicated for positioning can be printed orembossed on a surface of the cartridge, e.g., the cartridge underside.

At step 630, if the cartridge is inserted properly or fully into theanalyzer, one or more actions may be triggered. For example, if thecomputing device determines that the cartridge is inserted properly orfully into the analyzer, then the computing device may initiate a testcycle for the cartridge. At step 635, if the cartridge is not insertedproperly or fully into the analyzer, one or more alternative actions maybe performed. For example, if the cartridge is not inserted properly orfully into the analyzer, then the computing device may send anotification to the operator and/or prevent initiation of the test cyclefor the cartridge.

In a similar aspect, vibration profiles for one or more other processsteps, e.g., pneumatic pumping, may be obtained and compared with apre-established vibration profile, e.g., pre-established pneumaticpumping profile, and a band of expected variation (e.g., a predeterminedrange of acceptable variation) stored in the memory to determine whetherthe cartridge is being operated properly, e.g., whether the sampleand/or wash or calibration fluid is being properly pumped duringoperation. In this example, if an improper pumping operation isdetected, a user notification may be triggered and/or other correctivemeasures may be undertaken by the device to take into account theimproper pneumatic pumping profile.

Data Entry Using Acceleration Data

In one embodiment, the analyzer comprises an I/O interface for dataentry, as discussed above with respect to FIGS. 1A-1C. Specifically, aresistive touch-screen overlaid on the display and the external barcodescanner can be used for data entry, as shown in FIGS. 1A-1C. The barcodescanner is used to scan user and patient IDs, cartridge lots and types,control fluid lots, etc. During the interactive phase of the workflow,the operator responds to prompts displayed on the screen and selects thedesired options by touching the screen directly. In addition to thesetwo main methods, the accelerometers may also be used by the operator toenter data or trigger functions (e.g., a sequence of actions).

For example, the accelerometer may be configured to detect dynamic andstatic acceleration of the analyzer in space. During a learning session,the computing device may be configured to record the dynamic and staticacceleration of the analyzer, e.g., motion characteristics associatedwith waving or shaking the analyzer. The motion sequences orcharacteristics of the analyzer associated with the recorded dynamic andstatic acceleration are then saved in the memory for future use as areference. Thereafter, the operator may reproduce the specific motionsequences or characteristics in a normal operating mode of the analyzer.The computing device may detect the specific motion sequences orcharacteristics and compare the specific motion sequences orcharacteristics with reference sets of motion sequences orcharacteristics that are stored in the memory. Recognition of the motionsequences or characteristics by the computing device may trigger one ormore actions. For example, a specific predetermined sequence of motionssuch as a quick shaking of the instrument can be used to trigger actionssuch as “scroll to next page” or “initiate a power ON cycle.”

In another example, the accelerometer can be used to detect a vibrationsignature associated with gentle tapping, or tapping sequences, on theanalyzer casing. During a learning session, the computing device may beconfigured to record the static and dynamic acceleration of theanalyzer, e.g., vibration characteristics associated with tapping on theanalyzer. The vibration characteristics are then stored in the memoryfor future use as a reference. Thereafter, the operator may reproducethe specific tapping sequence in a normal operating mode of theanalyzer. The computing device may detect and compare the operatortapping with reference sets of tapping that are stored in the memory.Recognition of the motion or tapping sequences by the computing devicemay trigger a series of actions, including authorize operator access tothe system, system activation or deactivation (e.g., placing theanalyzer in OFF, sleeping or standby states), initiation of datadownload, initiation of a pre-set customizable series of actions, andinitiation of network connection or connection with other devices.Optionally, the analyzer display screen may also be used to perform someof these functions. If the display screen is used, sliding gestures maybe also used. Accordingly, aspects of the present invention provide asystem and processes for data entry into the analyzer using theaccelerometers.

As shown in FIG. 12, the process 700 may start at step 705 where anoperator triggers a training mode of the analyzer. For example, theoperator may use the I/O interface to trigger a training mode of theanalyzer whereby an interactive learning session may be initiated forteaching the analyzer motion sequences or characteristics. At step 710,the operator may specify a specific function to be initiated upon entryof specific motion sequences or characteristics. For example, theanalyzer may be configured to trigger actions such as “scroll to nextpage” or “initiate a power ON cycle” upon receiving specific motionsequences or characteristics. At step 715, the specific motion sequencesor characteristics may be recorded by the analyzer and saved in thememory. For example, the computing device may be configured to collectstatic and/or dynamic acceleration data during a recording session andsave the acceleration data as a specific profile of motion sequences orcharacteristics.

At step 720, the operator may trigger a normal operating mode of theanalyzer. At step 725, motion sequences or characteristics may beinitiated by an operator, and the initiated motion sequences andcharacteristics may be detected by the accelerometer and/or computingdevice. For example, the operator may repeat substantially the samemotion sequences or characteristics previously recorded in step 715, andthe repeated motion sequences and characteristics may be detected by theaccelerometer and/or computing device. At step 730, the initiated motionsequences or characteristics may be compared to a stored archive ofprofiles of motion sequences or characteristics. For example, thecomputing device may be configured to compare the initiated motionsequences or characteristics to the profiles of motion sequences orcharacteristics stored in the memory to determine whether the initiatedmotion sequences or characteristics have been assigned to trigger afunction of the analyzer. At step 735, if the initiated motion sequencesor characteristics are recognized and have been assigned to trigger afunction of the analyzer, the function may be triggered. For example, ifthe initiated motion sequences or characteristics match the profile ofmotion sequences or characteristics stored in the memory, then thecomputing device may execute or initiate the function assigned to theprofile of motion sequences or characteristics stored in the memory.

At step 740, if the initiated motion sequences or characteristics do notmatch a profile of motion sequences or characteristics stored in thememory, the process continues monitoring starting at step 725.

Initiating a Predetermined Sequence of Events Using Acceleration Data

In one embodiment, a state of the analyzer may be inferred by theacceleration data and used to trigger a predetermine sequence of events.For example, typically an external simulator may be inserted into theport of the analyzer at specific time intervals, e.g., once a week. Theexternal simulator helps determine if calibration of thermistors of theanalyzer has drifted such that the thermistors are out of specification.This may be performed by thermally shorting the thermistors andcomparing their outputs. If their outputs match, then the thermistorsare synchronized. However, the functionality of the external simulatormay be replaced by sampling the accelerometer data to identify a longperiod of time where the analyzer has been undisturbed. This impliesthat the two thermistors would be at thermal equilibrium.

In another example, the acceleration data can be used to identify longstretches of time when the analyzer is typically not disturbed, such asbetween midnight and 3 am, e.g., a time convenient for the user. Thecomputing device may be configured to perform housekeeping activities(such as downloading software updates) during such time. Accordingly,some aspects of the present invention provide systems and processes forinitiating a predetermined sequence of events using the accelerationdata.

As shown in FIG. 13, the process 800 may start at step 805 whereacceleration data is collected. For example, the accelerometer may beconfigured to collect static and/or dynamic acceleration dataintermittently or continuously throughout the day. At step 810, theacceleration data is used to determine the spatial orientation of theanalyzer and/or whether there is any movement of the analyzer. At step815, the determined spatial orientation and/or motion and/or rate ofmotion of the analyzer is compared to predetermined threshold(s). Forexample, the spatial orientation and/or motion and/or rate of motion ofthe analyzer are compared to predetermined threshold(s) stored in thememory to determine whether the analyzer is in motion or not.

At step 820, if the spatial orientation and/or motion and/or rate ofmotion of the analyzer exceed the predetermined threshold(s), the eventis time stamped and logged in a table or database within the memory. Forexample, if the computing device determines that the spatial orientationand/or motion and/or rate of motion of the analyzer exceed thepredetermined threshold(s), then the computing device may determine thatthe analyzer is being moved and/or transported, and time stamp and logthe event in a table or database such that the data is available forsubsequent determinations.

At step 825, if the spatial orientation and/or motion and/or rate ofmotion of the analyzer do not exceed the predetermined threshold(s), theevent is time stamped and logged in a table or database within thememory. For example, if the computing device determines that the spatialorientation and/or motion and/or rate of motion of the analyzer does notexceed the predetermined threshold(s), then the computing device maydetermine that the analyzer is stationary, and time stamp and log theevent in a table or database such that the data is available forsubsequent determinations.

At step 830, the time stamped events logged in the table and databaseare compared to a table or database including specific times of theday/month/year and/or specific states of operation for the analyzerduring which associated predefined events or sequences of events maytake place. At step 835, if the time stamped events logged in the tableand database are indicative of a specific time of the day/month/yearand/or a specific state of operation for the analyzer, then thecomputing device may initiate the associated predefined events orsequences of events. For example, the computing device may be configuredto identify a long period of time where the analyzer has beenundisturbed (a state of operation) and initiate a recording in thememory that the thermistors are at thermal equilibrium and/or identify along stretch of time when the analyzer is typically not disturbed,confirm that the analyzer has been undisturbed for a predeterminedamount of time (a state of operation), and download software updates.

At step 840, if the time stamped events logged in the table and databaseare not indicative of specific times of the day/month/year and/or aspecific state of operation for the analyzer, the process continuesmonitoring starting at step 805.

Detection of Free Fall

In one embodiment, the analyzer comprises free fall detectioncapabilities such that the detection of free fall may be used to triggerone or more actions by the computing device. For example, the ADXL345accelerometer features built-in free fall detection. FDA publication of30 Jan. 2008 entitled “Recommendations Clinical Laboratory ImprovementAmendments of 1988 (CLIA) waiver applications for Manufacturers of InVitro Diagnostics Devices” recommends including lock-out functions thatdo not allow output of results if the device was mishandled (e.g.dropped) and the device detects damage during internal electronic systemchecks. Many institutional users of point-of-care devices require thatperformance verification tests should be performed if an analyzer isdropped. Without means of automated free fall detection, meeting thisrequirement is dependent on self-reporting of the event by the operator.However, a point-of-care instrument equipped with an accelerometer maybe configured to make the determination, reporting, and performance ofthe verification itself.

Furthermore, the computing device may also be configured such that theanalyzer performs impact reducing actions upon the detection of a freefall. For example, the computing device may be configured to retractactuators in the measurement module and/or turn off the power to thedisplay to reduce the effect of the impact on the analyzer. Accordingly,some aspects of the present invention provide systems and processes fordetecting free fall of the analyzer and triggering one or more actionsif the analyzer is currently in free fall or has experienced a free fallevent.

As shown in FIG. 14, the process 900 may start at step 905 whereacceleration data is collected. For example, the accelerometer may beconfigured to collect static and/or dynamic acceleration dataintermittently or continuously throughout the day. At step 910, theacceleration data is used to detect whether the analyzer is in free fallor has undergone free fall followed by a subsequent impact. For example,the computing device may be configured to use the acceleration datacollected to determine whether the accelerometer senses free fall as apredetermined value (e.g., zero or g₀) and a sudden change inacceleration caused by the subsequent impact. The accelerometer readsonly the gravitational acceleration when the instrument is at rest. Ifthe instrument is dropped from a surface of a table or while beingcarried by a user, the accelerometer senses the free fall as apredetermined value (e.g., zero or close to zero within prespecifiedlimits). A sudden change in acceleration is observed when the analyzerimpacts the floor. Thus, the free fall and subsequent impact create aplateau and spike profile on a graph of the acceleration data over timethat can be interpreted by the computing device as the detection of afree fall occurrence (as shown in FIG. 15). A different profile ofacceleration is observed if the analyzer undergoes accidental impact,such as the operator inadvertently hitting the analyzer on the corner ofa table while carrying the analyzer (as shown in FIG. 16).

Optionally at step 915, if the analyzer is detected as currently beingin a state of free fall, the computing may be configured to perform oneor more actions to reduce the effect of the impact on the analyzer andreduce the risk of injury to the operator. For example, upon thedetection that the analyzer is currently in free fall, the computingdevice may be configured to retract actuators in the measurement moduleand/or turn off the power to the display.

At step 920, if the analyzer is detected as having been in a state offree fall and suffered a subsequent impact, the computing may beconfigured to perform one or more actions. For example, upon thedetection that the analyzer has experienced a free fall event, thecomputing device may be configured to lock the analyzer from operation,send an alert or notification the operator (e.g., provides anotification on the display or sends a notification to the operator or adesignator person via wireless connectivity), perform a systemdiagnostics, time-stamp when the analyzer is locked, perform a systemverification in accordance with regulatory requirements, time-stamp whenthe system verification is performed, store the time-stamps in anelectronic auditable system, determine whether the system performanceverification fails, and/or communicate the failure of the systemperformance verification to the electronic auditable system.

In additional embodiments, the electronic auditable system may beconfigured to perform replacement of the analyzer, and the computingdevice may be configured to display a status of the replacement on theanalyzer. Further, the computing device may be configured to communicateautomatically and wirelessly an operational status of the analyzer to aremote entity, e.g., a predetermined person at a hospital. The alert mayinclude a visual alarm, an audible alarm, a notice on a display screenof the analyzer, and a message sent wirelessly to a predeterminedentity, e.g., a person responsible for integrity of the system, adistributor of the system, and/or a manufacturer of the system.

At step 925, if the acceleration data is not indicative of theoccurrence of a free fall event, the process continues monitoringstarting at step 905.

Detection of Properly Functioning Analyzer

In one embodiment, the analyzer comprises electromechanical features forperforming a test cycle on the cartridge, as discussed above withrespect to FIGS. 1A-1C. Specifically, the measurement module thatinterfaces with the cartridge moves multiple plungers in predeterminedtrajectories when the analyzer runs a specific cartridge (assay). Thisactuation creates a vibration profile 1005 for a typical cartridge (asshown in FIG. 17). Around the vibration profile of the typicalcartridge, there is a band of expected variation 1010 that representsmanufacturing variation (of the cartridge and/or analyzer),environmental variation, etc. After a cartridge is run, the vibrationprofile of that cartridge 1015 can be compared with the typical profile1005 for a similar cartridge. Deviations from the typical profile 1005may be used to indicate conditions that could require preventivemaintenance. For example, a deviation from the typical profile 1005could indicate parts about to get loose in the analyzer that wouldeventually require preventive maintenance. Accordingly, some aspects ofthe present invention provide systems and processes for detectingwhether the analyzer is functioning properly using vibration profiles.

Furthermore, the measurement module may also be equipped with anelectromechanical contact switch triggered by the cartridge when thecartridge is inserted in the correct position in the port. The computingdevice monitors the switch status and initiates the cartridge test cyclewhen the switch is activated. Similarly, the computing device may beconfigured to detect removal of the cartridge. However, theelectromechanical features described above require additional parts(e.g., follower arm, electromechanical switch, cables, and connectors)and additional features on the measurement module mechanical housing toguide the follower arm and position the switch. These parts and featuresmay be potentially eliminated by using acceleration data.

For example, engagement of a cartridge latch when the cartridge is fullyinserted in the analyzer creates a signature vibration profile that canbe detected by the accelerometer(s). The computing device may beconfigured to compare the vibration profile for an inserted cartridge toa pre-established vibration profile stored in the memory to determinewhether proper or full engagement of the cartridge has occurred.Accordingly, aspects of the present invention provide a system andprocesses for determining whether the analyzer is functioning properlyusing vibration profiles.

As shown in FIG. 18, the process 1100 may start at step 1105 where adetermination is made as to whether the analyzer has been requested tostart a test cycle for an analytical test. At step 1110, accelerationdata is collected during the test cycle. For example, the accelerometermay be configured to collect static and/or dynamic acceleration data. Atstep 1115, the acceleration data is used to create an accelerationprofile for the test cycle of the cartridge. For example, the computingdevice may be configured to use the acceleration data collected duringthe test cycle of the cartridge, which comprises vibrationscharacteristic of the electromechanical interaction between thecartridge and the analyzer during the test cycle, to create a vibrationprofile for the test cycle of the cartridge.

At step 1120, the vibration profile for the test cycle of the cartridgemay be compared to a pre-established vibration profile, e.g., avibration profile pre-recorded for a proper test cycle of a similarcartridge with the same analyzer. For example, as shown in FIG. 17, thecomputing device may be configured to compare the vibration profile 1015to the pre-established vibration profile 1005 and the band of expectedvariation 1010 (e.g., a predetermined range of acceptable variation) todetermine whether the analyzer is functioning properly.

At step 1125, if the analyzer is functioning properly, one or moreactions may be triggered. For example, if the computing devicedetermines that the analyzer is functioning properly, then the computingdevice may log the event or send a notification to the operator. At step1130, if the analyzer is not functioning properly, one or morealternative actions may be performed. For example, if the analyzer isnot functioning properly, then the computing device may send anotification to the operator, perform system maintenance, and/or preventreporting of the test result.

Combining Data Input Received from a Multitude of Sensors to AchieveVarious Objectives

In additional or alternative embodiments, the analyzer compriseson-board sensors additional to that of the accelerometers 25 forperforming a test cycle on the cartridge, as discussed above withrespect to FIGS. 1A-1C. Specifically, the program code of the analyzer10 may collect data acquired at any time from one or more on-boardsensors, e.g., a temperature sensor, an ambient light sensor, abarometric pressure sensor, an imaging camera, etc. The collected datamay be used by the analyzer 10 alone or in combination with theacceleration and/or inertial data collected by the accelerometers forvarious functions of the analyzer. For example, the measurement of thetemperature and barometric pressure during the test cycle may also beused as correction factors for the generation of assay results. Thetemperature sensors may also be used to measure the ambient temperatureat the time of testing, and the collected ambient temperature data mayalso be used by the analyzer to prevent the delivery of results if themeasured ambient temperature is outside of an operational range.Measurement of the ambient light may be used to automatically adjust theillumination intensity of the analyzer display. Moreover, the imagingcamera may be configured to read the barcodes on the cartridges.

The data collected by the on-board sensors and the acceleration and/orinertial data collected from the accelerometers may have additional usesif communicated to a central device, e.g., a central computer server,where the collected data from the on-board sensors and accelerometersmay be further analyzed and processed into actionable information. Theactionable information may then be used by customers and/or additionalentities such as R&D personnel, Technical Support services, andMarketing in support of the IVD instrument system. For example, theactionable information may be used to obtain a better characterizationof the environments where the analyzers are used as a source ofinformation for the investigation of customer issues, and for designinputs relevant to design enhancements or future designs of the IVDinstrument system. Examples of the data that may be useful include: (i)ambient temperature extremes and averages, (ii) average barometricpressure and extremes, and (iii) lighting environments, includingdetermination of artificial and natural light. This data may be usedindividually, or in combination with other sources of information, suchas the acceleration and/or inertial information (collected from theaccelerometers) and cartridge consumption information (as described injointly owned U.S. Pat. No. 7,263,501, which is incorporated herein byreference in its entirety), to determine usage patterns for customerfacilities.

Advantageously, various aspects of the invention described hereinprovide for systems and processes capable of (a) detection of mechanicalabuse or potentially abusive vibration, shock or motion imposed on theanalyzer, (b) enhanced power management and potential extension ofbattery life on a single charge, (c) elimination or reduction of someelectromechanical features, (d) enhancement of user interface, and (e)elimination or detection of artifacts due to uncontrolled motion of thebiological sample fluid in a test cartridge during the testing cycle byusing an internal motion sensor (accelerometer or other) to detectdisadvantageous motion or angle changes from an ideal position.

For purposes of illustration and not limitation, the following examplesprovide information on the effect of inclination changes, cellsedimentation, and non-homogeneity of cells in a hematocrit assay.

EXAMPLE 1

The present example characterizes the effect that analyzer orientationmay have on a hematocrit assay measurement especially for blood sampleswith a low hematocrit and a high sedimentation rate.

Patient blood samples from a variety of units in a hospital werecollected. Upon the arrival of each sample to the lab, approximately 1ml of blood was drawn from the sample tube and placed in a plain tubefor use in the present example. Relevant sample identificationinformation including sample code and unit code were recorded. Thesample was mixed with a roller mixer for at least five minutes and thentested with four analyzers, two of which were positioned at level (0°)and two positioned at a 45° pitch angle. The cartridges used for thestudy were CHEM6+(which measures glucose, urea, sodium, potassium,chloride and hematocrit) and CHEM8+(which measures glucose, creatinine,urea, total carbon dioxide, sodium, potassium, calcium, chloride andhematocrit.

If the hematocrit values from the two tilted analyzers were differentfrom those of the two level analyzers by 2% packed cell volume (PCV) ormore, further testing was performed on the sample. Hematocritmeasurements under a variety of analyzer pitch angles (0°, ±30°, ±45°,±60°), spun hematocrit, and an improvised “Micro” erythrocytesedimentation rate (ESR) were further investigated.

Among 169 samples, 18 showed some different results between level (0°)and 45°, and the samples were tested further under various analyzerpitch angles (0°, ±30°,145°, ±60°). For each pitch angle, the averagehematocrit of each pair of analyzers was calculated. The highest and thelowest hematocrit values and the related pitch angles were extracted.The difference between the highest hematocrit value and the lowesthematocrit value of each sample is included in Table 1 below. Aregression between hematocrit value and pitch angle was performed foreach of the 18 samples and the regression slope is listed in Table 1 aswell.

The maximum difference between the highest and the lowest hematocrit was7.2% PCV observed from Sample No 4. The highest hematocrit occurred at−45° (analyzer head down) and the lowest hematocrit occurred at +60°(analyzer head up). All the samples in Table 1 showed the same trend,that is, the highest value was observed at a head down position and thelowest observed at a head up position, which is also demonstrated by thenegative regression slopes. Accordingly, the following conclusions weredrawn from the data obtained: hematocrit measured with the analyzer maybe affected by analyzer pitch angles during blood measurement forpatient blood samples with low hematocrit value and high sedimentationrate. The hematocrit value may read lower with the analyzer tilted upand read higher with the analyzer tilted down.

TABLE 1 Highest Lowest Hct. Regres- Sam- Hct. Pitch Hct. Pitch Differ-sion ple Value Angle Value Angle ence Slope No. (% PCV) (°) (% PCV) (°)(% PCV) (% PCV/°) 4 23.2 −45 16.0 60 7.2 −0.0621 32 25.0 −45 19.5 45 5.5−0.0409 49 23.2 −60 19.5 60 3.7 −0.0276 51 20.5 −30 17.9 45 2.6 −0.017858 25.8 0 23.3 60 2.5 −0.0157 60 25.3 −30 20.6 60 4.7 −0.0282 65 25.7−60 23.3 60 2.4 −0.0207 92 32.8 0 30.3 45 2.5 −0.0560 97 22.6 −60 20.760 1.9 −0.0164 101 28.2 −60 25.8 45 2.4 −0.0157 102 23.4 −45 20.3 45 3.1−0.0216 115 26.1 −45 20.6 60 5.5 −0.0356 116 28.7 −30 25.6 45 3.1−0.0225 123 30.9 −45 27.9 45 3.0 −0.0163 129 28.2 −45 26.1 45 2.1−0.0152 135 27.0 −45 24.9 60 2.1 −0.0135 154 26.5 −45 24.3 60 2.2−0.0198 164 25.9 −60 21.8 45 4.1 −0.0298

EXAMPLE 2

The present example characterizes the effect pitch angle and/or rollangle may have on a hematocrit assay measurement especially for bloodsamples with a low hematocrit and a high sedimentation rate.

Patient blood samples were collected. Each sample was centrifuged at5000 rpm for 5 minutes to separate plasma and blood cells. The plasmaand blood cells were then reconstituted to obtain a sample of 18% PCVand ±2% PCV. The sample was then tested with analyzers at a verticalpitch between +45° and −45°. If the sample exhibited significantorientation effect, as described above with respect to Example 1, thenthe sample was set aside for further testing. The further testingincluded testing the sample with analyzers at a 0° and ±20° pitch angle(−20° referring to a head-down tilt and +20° referring to a head-uptilt), 0° and ±20° roll angle (−20° referring to a left angle tilt and+20° referring to a right angle tilt), and a compound angles (pitch &roll). The cartridges used for the study were E3+(which tests sodium,potassium and hematocrit) and CHEM8+.

In a total of five donors that were tested, two did not show significantdifferences between +45° and −45° analyzer angles, and thus thesesamples were discarded. The remaining three samples were used tocomplete the study, and the relevant data is summarized below in Table2. Among all test events (various angles of pitch and roll) only onesample (Sample 3 at a pitch angle of −20° and a roll angle of 0° (Event11)) demonstrated a hematocrit bias value greater than allowed error.However, this anomaly may have been the result of a spuriousexperimental error unrelated to analyzer angle. All other results werewithin allowed error. Accordingly, the following conclusions were drawnfrom the data obtained: the analyzer orientation effect on hematocritresults is unlikely to give rise to clinically significant errors whenthe analyzer is maintained to within ±20° of level.

TABLE 2 Mean Hematocrit Bias of each event of each event Event PitchRoll Sam- Sam- Sam- Sam- Sam- Sam- No. Angle Angle ple 1 ple 2 ple 3 ple1 ple 2 ple 3 1 45 0 14.8 15.0 17.4 2 −45 0 16.7 19.4 22.0 3 20 −20 15.817.7 17.0 −0.6 0.2 −1.4 4 0 10 16.8 18.0 18.4 0.4 0.5 −0.1 5 0 −20 16.316.8 17.8 −0.1 −0.7 −0.6 6 −20 20 16.9 18.4 18.9 0.5 0.9 0.5 7 0 −1017.2 17.1 18.4 0.9 −0.4 −0.1 8 −20 −20 16.3 17.3 18.3 −0.1 −0.2 −0.1 9 020 15.7 17.6 18.6 −0.7 0.1 0.2 10 20 0 16.1 17.2 17.0 −0.3 −0.3 −1.4 11−20 0 16.9 17.7 21.9 0.5 0.2 3.5 12 0 0 16.5 — 18.5 0.1 — 0.0 13 20 2016.9 17.2 18.0 −0.5 −0.3 −0.5 14 −10 0 16.5 17.2 18.6 0.1 −0.3 0.2 15 100 16.0 17.6 18.3 −0.3 0.1 −0.1 16 −45 0 17.6 18.3 23.1 17 45 0 15.7 16.113.2

While the invention has been described in terms of various preferredembodiments, those skilled in the art will recognize that variousmodifications, substitutions, omissions and changes can be made withoutdeparting from the spirit of the present invention. It is intended thatthe scope of the present invention be limited solely by the scope of thefollowing claims. In addition, it should be appreciated by those skilledin the art that a plurality of the various embodiments of the invention,as described above, may be coupled with one another and incorporatedinto a single reader device.

We claim:
 1. A portable clinical system for performing a hematocritanalysis, the system comprising: a test device comprising a hematocritsensor configured to perform the hematocrit analysis, which includesgenerating an electric signal based on a hematocrit measurement of abiological sample; and an analyzer comprising: a port configured toreceive the test device; and a computing device configured to: initiatea test cycle of the test device, the test cycle including performance ofthe hematocrit analysis; determine spatial orientation of the analyzerduring the test cycle of the test device; compare the determined spatialorientation to a threshold operating spatial plane for the test device;and when the determined spatial orientation exceeds the thresholdoperating spatial plane, provide an alert prompting a user to takecorrective action, wherein the corrective action is taken withoutreinitiating the test cycle including the performance of the hematocritanalysis.
 2. The system of claim 1, wherein the computing device isfurther configured to suppress the result of the hematocrit analysis,when the determined spatial orientation exceeds the threshold operatingspatial plane.
 3. The system of claim 1, wherein the computing device isfurther configured to correct the result of the hematocrit analysis,when the determined spatial orientation exceeds the threshold operatingspatial plane.
 4. The system of claim 1, wherein the providing the alertprompting the user to take the corrective action comprises displayingthe alert on the analyzer and the alert instructs the user to move thespatial orientation of the analyzer below the threshold operatingspatial plane.
 5. The system of claim 1, wherein: the providing thealert prompting the user to take the corrective action comprisesdisplaying the alert on the analyzer and the alert instructs the user tomove the spatial orientation of the analyzer below the thresholdoperating spatial plane; and the computing device is further configuredto: detect a change in the spatial orientation of the analyzer duringthe test cycle; determine a new spatial orientation of the analyzer;compare the determined new spatial orientation to the thresholdoperating spatial plane; and complete the test cycle and provide theresult of the hematocrit analysis when the determined new spatialorientation is below the threshold operating spatial plane.
 6. Thesystem of claim 1, wherein: the analyzer further comprises a base havinga horizontal plane; and the threshold operating spatial plane is no morethan about ±15° from the horizontal plane of the base.
 7. The system ofclaim 6, wherein the threshold operating spatial plane is no more thanabout 10° from the horizontal plane of the base.
 8. The system of claim1, wherein the hematocrit sensor is a conductivity sensor.
 9. The systemof claim 1, wherein: the analyzer further comprises a base having ahorizontal plane; the port is substantially aligned to a first planeparallel to the horizontal plane of the base; and the hematocrit sensoris substantially aligned to a second plane parallel to the horizontalplane of the base.
 10. The system of claim 9, wherein the thresholdoperating spatial plane is no more than about 15° from the horizontalplane of the base.
 11. The system of claim 10, wherein: the providingthe alert prompting the user to take the corrective action comprisesdisplaying the alert on the analyzer and the alert instructs the user tomove the spatial orientation of the analyzer below the thresholdoperating spatial plane; and the computing device is further configuredto: detect a change in the spatial orientation of the analyzer duringthe test cycle; determine a new spatial orientation of the analyzer;compare the determined new spatial orientation to the thresholdoperating spatial plane; and complete the test cycle and provide theresult of the hematocrit analysis when the determined new spatialorientation is below the threshold operating spatial plane.
 12. Thesystem of claim 1, wherein the computing device is further configuredto: determine motion of the analyzer during the test cycle of the testdevice; compare the determined motion to a threshold rate of motion forthe test device; and at least one of (i) provide a different alertprompting the user to take different corrective action during the testcycle, (ii) correct the result of the hematocrit analysis, and/or (iii)suppress the result of the hematocrit analysis, when at least one of:(i) the determined spatial orientation exceeds the threshold operatingspatial plane, and/or (ii) the determined motion exceeds the thresholdrate of motion.
 13. The system of claim 12, wherein the threshold rateof motion is no more than about 50 meters/second².
 14. The system ofclaim 1, wherein the computing device comprises at least oneaccelerometer and is further configured to measure static accelerationon at least three axes to determine the spatial orientation of theanalyzer.
 15. The system of claim 1, wherein the computing device isconfigured to measure static acceleration on at least three axes of theanalyzer to determine the spatial orientation of the analyzer, and thedetermining the spatial orientation comprises determining at least oneof roll, pitch, and yaw of the analyzer based on the measured staticacceleration on the at least three axes of the analyzer.
 16. A method ofperforming a hematocrit analysis, the method comprising: inserting atest device comprising a hematocrit sensor into a port of an analyzer;initiating, by the analyzer, a test cycle of the test device, the testcycle including performance of the hematocrit analysis, wherein theperformance of the hematocrit analysis includes the test devicegenerating an electric signal based on a hematocrit measurement of abiological sample; determining spatial orientation of the analyzerduring the test cycle of the test device; comparing the determinedspatial orientation to a threshold operating spatial plane for the testdevice; and when the determined spatial orientation exceeds thethreshold operating spatial plane, providing an alert prompting a userto take corrective action, wherein the corrective action is takenwithout reinitiating the test cycle including the performance of thehematocrit analysis.
 17. The method of claim 16, further comprisingcorrecting a result of the hematocrit analysis, when the determinedspatial orientation exceeds the threshold operating spatial plane. 18.The method of claim 16, further comprising suppressing the result of thehematocrit analysis, when the determined spatial orientation exceeds thethreshold operating spatial plane.
 19. A portable clinical system for invitro analysis, the system comprising: a test device comprising at leastone sensor configured to output a signal that is partially dependent onnon-homogeneity of cells in a blood sample positioned in a region of theat least one sensor; and an analyzer comprising: a port configured toreceive the test device; and a computing device configured to: initiatea test cycle of the test device that includes output of the signal;determine spatial orientation and motion of the analyzer during the testcycle of the test device, the test cycle including performance of ahematocrit analysis: compare the determined spatial orientation to athreshold operating spatial plane for the test device; compare thedetermined motion to a threshold rate of motion for the test device; andwhen at least one of (i) the determined spatial orientation exceeds thethreshold operating spatial plane, and/or (ii) the determined motionexceeds the threshold rate of motion, provide an alert prompting a userto take corrective action, wherein the corrective action is takenwithout reinitiating the test cycle including the performance of thehematocrit analysis.
 20. The system of claim 19, wherein the computingdevice is further configured to suppress the result of the hematocritanalysis, when at least one of: (i) the determined spatial orientationexceeds the threshold operating spatial plane, and/or (ii) thedetermined motion exceeds the threshold rate of motion.
 21. The systemof claim 19, wherein the computing device is further configured tocorrect the result of the hematocrit analysis, when at least one of: (i)the determined spatial orientation exceeds the threshold operatingspatial plane, and/or (ii) the determined motion exceeds the thresholdrate of motion.